Current methods to determine the structure of organic molecules, rely on solid-state structure determination, usually using X-ray crystallography, providing determination of both connectivity and 3-dimensional structure (stereochemistry). In this case a crystal of the material must be available—by no means a given. Also, the structure of the molecule may be affected by the crystalline lattice into which it must conform, hence the determination may be less accurate when compared to solution-based activities.
Alternatively, structure determination may involve mainly spectroscopic techniques, including NMR spectroscopy.
Elyashberg et at (Journal of Analytical Chemistry 63 (1) (2008) p 13-20) discuss an expert system which makes use of a comparison with a large database (400,000 molecular structures and 13C and 1H NMR spectra) in order to determine molecular structures.
Reggelin et at (Angew. Chem. Int. Ed. Engl. (1994) 33 (7) p 753 to 755) discuss determination of relative configuration by distance geometry calculations from NOESY spectra.
Kock et at (Magn. Reson. Chem. (2004) 42 pp 1042-1045) discuss a method for structure elucidation involving generating all possible structures for a given molecule and comparing the predicted NMR spectra of these structures to the experimentally determined spectra.
Mierke et at (J. Org. Chem. 57 (23) (1992) pp 6365 to 6367) discuss determination of conformation and configuration using NOESY data.
Typically in such a structure determination, a trained chemist or spectroscopist makes a large number of qualitative assessments of spectroscopic properties of the molecule, or its component parts, and combines these with chemical knowledge and spectroscopic experience in order to find an answer which best fits the information available. An often unreliable automated alternative to finding connectivity is for the spectroscopic information to be input to an algorithm which makes the qualitative assessments on the basis of comparison with databases of known compounds and spectra. In these cases, the determination of structure is severely limited by the skill and knowledge of the spectroscopist and the quality of the database and searching algorithms. Compiling databases of structures and spectra is extremely time-consuming and expensive. The method involves comparing spectra with known phenomenon. If a new class of material is studied, this can severely compromise the likelihood or accuracy of structure elucidation. Also, 3-dimensional structure information requires the most detailed analysis of spectra. The spectroscopist must specify a series of experiments usually NOE (Nuclear Overhauser Effect) and/or ROE (Rotational Overhauser Effect) and/or RDC (Residual Dipolar Coupling) targeting 3-D (stereochemical) information, or else undertake a significant analysis of coupling information. Neither of these investigations is by any means guaranteed to work, and depends very strongly upon the nature of the material studied.
There is a need for a method for determining molecular structure which overcomes the problems of the prior art.